The primary mechanism where by insulin stimulates glucose transport activity involves translocation of the glucose transporter from an intracellular compartment to the plasma membrane. Earlier work has demonstrated that lipolytic agents which stimulate adenylate cyclase, such as catecholamines and ACTH, inhibit insulin-stimulated glucose transport activity. This inhibition was reversed by antilipolytic agents such as adenosine, nicotinic acid, and prostaglandins which inhibit adenylate cyclase. These alterations in insulin-stimulated glucose transport activity occur through changes in the intrinsic activity of glucose transporters residing in the plasma membrane and are cAMP-independent. Present studies indicated that stimulatory and inhibitory receptor effects on insulin-stimulated glucose transporter activity are meditated by their associated GTP-binding proteins, Gs and G at the plasma membrane. The glucose transporters are direct targets for interation with the G-proteins. The results of studies with antibodies raised against various GTP-binding proteins indicate the presence of Gs as well as Gi and Go in the plasma membrane. However, insulin has no effect on the translocation of G proteins. Interestingly, PMA has an effect which is similar to insulin on the intrinsic activity of the glucose transporter residing in the plasma membrane. Some of these results have been presented at the ASBMB meetings (Fed. Proc. 49, 1990), and submitted for publication.